Approximately four and one half million people in the U.S. are afflicted with psoriasis. Psoriasis is a skin disease often confined to localized areas of skin. It is typified by dry, scaly skin, abnormal thickening of epidermis, and rapid cell turnover in the skin. Psoriasis can be exacerbated by external factors including sun exposure, viral infections, and corticosteroid or beta-blocker use. Histologically, it is characterized by abnormalities including keratinocyte hyperplasia, abnormal differentiation sequence of keratinocytes in affected epidermis, and accumulation of leukocytes within the epidermis (Wright and Camplejohn, Eds., Psoriasis: Cell Proliferation, (Churchill Livingstone, Edinburgh, 1983), pp. 147-295; Weinstein, et al., J. Invest. Dermatol., 85:579, 1985).
Other skin disorders characterized by skin cell hyperproliferation include actinic keratoses, seborrheic keratoses and skin cancers such as basal cell carcinoma.
Infection with papilloma viruses also causes skin cell hyperproliferation (Zur Hausen, Int. Rev. Exp. Path., 25:307-326 (1983); Pfister, Rev. Phys. Biochem. Pharmacol., 99:111-181 (1984). Infection of cervix by certain papilloma viruses has been strongly linked to a majority of cervical cancers, the second largest cause of cancer deaths in women worldwide (Parkin, et al., Cancer, 41:184-187 (1988); Durst, et al., Oncogene, 1:251-256 (1987); Broker and Botchan, Cancer Cells--DNA Tumor Viruses, New York: Cold Spring Harbor Laboratory, 1986).
Keratinocyte hyperplasia in psoriasis is linked to overproduction of cytokines such as TG.alpha. and interleukin-6 (IL-6) and overexpression of epidermal growth factor receptor (EGF-R) in affected skin (Krueger, et al., J. Invest. Dermatol., 94:1355-1405, 1990). EGF-R is a 180-kD cell-surface receptor whose activity is regulated by both EGF and TGF.alpha.. In psoriasis vulgaris, EGF-R persists throughout the epidermis from the basal layers to the stratum corneum. Such persistent EGF-R has been shown to be biologically active in vivo in nude mice (Nanney, et al., J. Invest. Dermatol., 98:296-301, 1992).
Suggested treatment for psoriasis includes direct inhibition of keratinocyte growth and inhibition of activated lymphocyte proliferation (Dvir et al., J. Cell Biol. 113:857-865, 1991). Many topical products currently available are irritating, messy or simply ineffective. Topical steroids account for 90% of the psoriasis market in the United States and have many side effects including cutaneous atrophy, telangiectasia, formation of striae and tachyphylaxis.